Phase 1, Single-Center, Dose-Escalating, Open-Label, Safety Clinical Trial of Parenteral Ascorbate-Meglumine as a Novel Magnetic Resonance Imaging (MRI)-Guided Adjunctive Therapeutic for Stereotactic Radiosurgery (SRS)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- LadeRx LLC
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Safety as measured by adverse events
研究概览
简要总结
Phase 1, Single-Center, Dose-Escalating, Open-Label, Safety Clinical Trial of Parenteral Ascorbate-Meglumine as a Novel Magnetic Resonance Imaging (MRI)-guided Adjunctive Therapeutic for Stereotactic Radiosurgery (SRS)
详细描述
Phase 1, single-center, open-label study in subjects receiving Stereotactic Radiosurgery (SRS) for brain metastases. The study will consist of 4 principal cohorts (n=3 in each cohort). Each cohort will receive an escalating dose of ascorbate-meglumine as an Magnetic Resonance Imaging (MRI)-detectable adjunctive therapeutic to SRS.
Subjects will complete a planning MRI for SRS with gadolinium- diethylenetriamine penta-acetic acid (GD-DPTA) per standard of care for SRS. Forty-eight hours after the planning MRI, the subjects will complete the study MRI with ascorbate-meglumine contrast agent. Each cohort will receive an escalating dose of ascorbate-meglumine by intravenous administration over 1 hour during the MRI. The total dose of ascorbate-meglumine will escalate from the first cohort to the next cohort in a sequential manner. During ascorbate-meglumine infusion, MRI scans will be performed to evaluate the contrast effect and PK blood draws will occur at defined time points.
Patients will return for the SRS procedure within 1 week following the planning MRI per standard of care. During SRS, subjects will receive a second dose of ascorbate-meglumine as an adjunctive therapeutic.
Patients will enter into a follow up phase within 2 weeks after the SRS procedure per standard of care.
The primary endpoint is to evaluate the safety of parenteral ascorbate-meglumine as a MRI-detectable adjunctive therapeutic to SRS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary cancer diagnosis with newly diagnosed brain metastases
- •Diagnostic MRI demonstrates the presence of 1 to 3 intact (not previously irradiated or resected) brain metastases.
- •Maximum tumor diameter ≤ 2.5 cm for the largest lesion determined during the planning MRI
- •Plan of care must include Stereotactic Radiosurgery (SRS)
- •SRS treatment plan must be delivered as a single RT fraction
- •Age 18 years and older
- •Life expectancy of at least 3 months
- •GPA score 0.5 or greater
- •Capable of providing written informed consent to participate in the study
排除标准
- •Primary lesion with radiosensitive histology (i.e., small cell carcinoma, germ-cell tumors, lymphoma, leukemia, and multiple myeloma)
- •Metastases in the brain stem, pons or medulla or within 3 mm of the optic apparatus (such that some portion of the optic nerve or chiasm would receive a radiation dose > 10 Gy SRS in one single fraction)
- •Previous whole-brain radiation (previous SRS to or resection of other brain lesions is permitted if more than 3 months prior to the date of enrollment on this protocol)
- •Pregnancy
- •History or manifestation of glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency
- •History of oxalate kidney stones
- •History of iron overload or hemochromatosis
- •History of allergy to ascorbic acid
- •Anuria, dehydration, serum albumin <3.0 g/dL, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated .
- •Subjects who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide.
- •Subjects who are on strong inducers, inhibitors or substrates of CYP within 3 days of planned administration of study ascorbate-meglumine.
- •Subjects for which MRI is contra-indicated (for example a pacemaker/recent surgery with orthopedic prosthesis)
研究组 & 干预措施
Ascorbate Meglumine dose 1
Patients receiving Stereotactic Radiosurgery (SRS) treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced Magnetic Resonance Imaging (MR) scan showing 1-3 brain metastases, including post-operative patients with 1-3 residual metastases. The first cohort of patients will receive ascorbate-meglumine at a dose administration rate of 0.16 g/min for 60 minutes.
Interventions:
Drug: Ascorbate-Meglumine
干预措施: Ascorbate-Meglumine (Drug)
Ascorbate Meglumine dose 2
Patients receiving SRS treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced MRI scan showing 1-3 brain metastases, including post-operative patients with 1-3 residual metastases.The second cohort of patients will receive ascorbate-meglumine at a dose administration rate of 0.31 g/min for 60 minutes.
Interventions:
Drug: Ascorbate-Meglumine
干预措施: Ascorbate-Meglumine (Drug)
Ascorbate Meglumine dose 3
Patients receiving SRS treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced MRI scan showing 1-3 brain metastases, includingpost-operative patients with 1-3 residual metastases. The third cohort of patients will receive ascorbate-meglumine at a dose administration rate of 0.63 g/min for 60 minutes.
Interventions:
Drug: Ascorbate-Meglumine
干预措施: Ascorbate-Meglumine (Drug)
Ascorbate Meglumine dose 4
Patients receiving SRS treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced MRI scan showing 1-3 brain metastases, includingpost-operative patients with 1-3 residual metastases. The fourth cohort of patients will receive ascorbate-meglumine at a dose administration rate of 1.25 g/min for 60 minutes.
Interventions:
Drug: Ascorbate-Meglumine
干预措施: Ascorbate-Meglumine (Drug)
结局指标
主要结局
Safety as measured by adverse events
时间窗: 1 week after receiving study drug with SRS
Adverse events will be monitored in patients receiving ascorbate-meglumine during Stereotactic Radiosurgery (SRS)
次要结局
未报告次要终点